Medical hypothesis discovery and innovation in ophthalmology

Tetracyclines, especially doxycycline, play a role in the regulation of inflammation, immunomodulation, cell proliferation, and angiogenesis. Treatment of corneal angiogenesis or choroidal neovascularization with tetracyclines has been shown to be effective in animal models. The aim of this study was to evaluate the efficacy of oral doxycycline in reducing the total number of intraocular injections needed for controlling neovascular age-related macular degeneration in human patients. In this interventional case series, 28 random consecutive patients with neovascular age-related macular degeneration from Farabi Hospital, Tehran, Iran were treated for 4 months with 200 mg doxycycline once a day after the first intravitreal bevacizumab injection in addition to standard therapy in agreement with as-needed regimen. After 12 months of follow-up, total number of injections, foveal thickness and visual acuity were compared to those at baseline and of similar studies. Similar to standard treatment, co-treatment with doxycycline was able to control active disease (intraretinal or subretinal collection or leakage, new-onset of macular hemorrhage, and depletion of visual acuity more than 5 letters based on Early Treatment Diabetic Retinopathy Study [ETDRS] charts) yet with fewer injections (for current study and standard treatment, respectively 3.14 vs. 5.92, P < 0.001). Furthermore, while better control of the foveal thickness was achieved (P < 0.001), vision improvement was similar to that achieved with standard therapy (P > 0.05). If confirmed in larger studies, the findings of this interventional case series could provide a strategy to control neovascular age-related macular degeneration with fewer intraocular bevacizumab injections by co-administering a well-known oral agent—doxycycline. 

Diabetic Retinopathy (DR) is the most prevalent health problem, which is influenced by environmental and genetic factors with an increasing prevalence. The current systematic review is focused on mtDNA modification, including polymorphism and mutation/deletion, with a direct effect on DR. This systematic search was initially done through PubMed, Cochrane, EMBASE, SCOPUS, and Web of Science without a restriction on the years of publication. The terms searched included ‘‘mtDNA’’, ‘‘mitochondrial DNA’’, ‘‘diabetes’’, ‘‘diabetic’’, ‘‘retina’’, and ‘‘diabetic retinopathy’’. Animal, cohort, cross-sectional, and in vitro studies, as well as case series, case reports, review articles, and Letters to Editor were excluded from this research. From 1528 resulting searched articles, only 12 papers were finally chosen as the case-control studies considering  mtDNA gene and DR. Actually, of these 12 articles, 8 studies were concerned with mtDNA polymorphisms (UCP1, UCP2, ROMO-1, and Mn-SOD) and 4 articles were related to mtDNA mutation (A3243G mutation in tRNALeu(UUR) gene and mtDNA deletion (ΔmtDNA 4977)). Some conflicting results were found between the selected genetic modifications of mtDNA, such as Mn-SOD, UCP1, ΔmtDNA 4977, tRNALeu (UUR), and ROMO-1. Finally, A3243G mutation in the tRNALeu (UUR) gene and rs660339 and V16A polymorphisms of UCP2 and Mn-SOD genes were respectively considered as the most important factors in the pathogenesis of DR. 

Timolol is a non-selective beta-adrenergic antagonist that is similar to propranolol. The mechanism through which these drugs act on the regression of neovascularization is largely unknown. However, it is thought that the drugs may act through vascular endothelial growth factor signaling, vasoconstriction, and vascular endothelial cell apoptosis. The aim of this study was to determine the effect of timolol on corneal neovascularization in rabbits. Neovascularization was induced in the eyes of 20 rabbits. Next, the rabbits were divided into two groups: the timolol (experimental) group received eye drops containing timolol 0.5% twice per day; and the saline (control) group received saline drops twice per day for two weeks. After 7 days, the mean area of corneal neovascularization (presented as a percentage relative to baseline) was significantly lower in the timolol group than in the saline group (4.63 ± 4.61% versus 58.39 ± 6.31%, P < 0.001). After 2 weeks, the mean area of corneal neovascularization was 0.85 ± 1.33% in the timolol group and 1.73 ± 2.06% in the saline group (P = 0.315). After the first week of treatment, timolol significantly reduced the area of neovascularization compared to control. Timolol may increase the rate of recovery from corneal neovascularization. 

Upper eyelid retraction is a characteristic feature of thyroid eye disease, including Graves’ orbitopathy. In this study, a new surgical technique for correction of lid retraction secondary to Graves’ orbitopathy is described. Sixteen eyelids of patients older than 18 years old underwent surgical correction for moderate to severe lid retraction secondary to Graves’ orbitopathy. In this procedure, levator aponeurectomy was performed via a transconjunctival approach. Upper marginal reflex distance (MRD1) was measured before the surgery and at 1 week, 3 months, and 6 months after the surgery. MRD1 was reduced significantly from preoperatively (mean: 7.84 mm) to 1 week after the surgery (mean: 3.59 mm) (P < 0.001). Three and six months after surgery, mean MRD1 was 5.09 mm and 5.10 mm, respectively, showing that lid retraction was improved significantly (P < 0.001). Lateral levator aponeurectomy via the transconjunctival approach is a simple, scar-less, quick procedure that has optimal stable outcome. 

The aim of this study was to analyze and compare corneal biomechanics in patients with bilateral keratoconus (KCN) with unilateral Vogt’s striae. In this prospective contralateral study, visual acuity, refraction, and corneal biomechanical parameters were evaluated in patients with bilateral KCN with unilateral Vogt’s striae using the Ocular Response Analyzer (ORA) (Reichert Inc., Buffalo, NY) and Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany). All patients underwent a comprehensive ophthalmic examination, including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction (calculated by vectorial analysis), slit-lamp biomicroscopy, and Scheimpflug-based tomography. The patients enrolled in this study had a reliable diagnosis of bilateral clinical KCN with unilateral Vogt’s striae based on slit-lamp signs as well as corneal topographic/tomographic maps.  Fifty patients aged 18 to 40 years were included in this study. There was a significant difference in all clinical (distance visual acuity and refraction) and corneal biomechanical parameters between KCN eyes with and without unilateral Vogt’s striae (all P < 0.05). However, there were no significant differences in peak distance (P = 0.291), corneal compensated intraocular pressure (IOPCC) (P = 0.08), and J45 (P = 0.131) between the two groups. Most corneal biomechanical parameters, except for peak distance, IOPCC, and J45, showed a significant difference between KCN eyes with and without unilateral Vogt’s striae. Vogt’s striae may cause corneal biomechanical deterioration. This information could be used in clinical practice. 

The aim of this study was to correlate macular thickness and visual field parameters in early glaucoma. A total of 104 eyes affected with early glaucoma were examined in a cross-sectional, prospective study. Visual field testing using both standard automated perimetry (SAP) and shortwave automated perimetry (SWAP) was performed. Global visual field parameters, including mean deviation (MD) and pattern standard deviation (PSD), were recorded and correlated with spectral domain optical coherence tomography (SD-OCT)-measured macular thickness and asymmetry. Average macular thickness correlated significantly with all measures of visual field including MD-SWAP (r = 0.42), MD-SAP (r = 0.41), PSD-SWAP (r = -0.23), and PSD-SAP (r = -0.21), with P-values <0.001 for all correlations. The mean MD scores (using both SWAP and SAP) were significantly higher in the eyes with thin than in those with intermediate average macular thickness. Intraeye (superior macula thickness – inferior macula thickness) asymmetries correlated significantly with both PSD-SWAP (r = 0.63, P < 0.001) and PSD-SAP (r = 0.26, P = 0.01) scores. This study revealed a significant correlation between macular thickness and visual field parameters in early glaucoma. The results of this study should make macular thickness measurements even more meaningful to glaucoma specialists.